The long-term objective of the study is to develop a novel anti- platelet agent that may be useful to prevent arterial reocclusion and restenosis in the event of angioplasty therapy for cardiovascular disorder. We have previously demonstrated in the Phase study that a particular analogue of diadenosine tetraphosphate (AP4A analogue-16) is the most promising inhibitor for adenosine-5'-diphosphate (ADP)-induced platelet activation in vitro, among various diadenosine tetraphosphate analogues studied. ADP, an agonist to blood platelet activation, has been known to play an important role in arterial thrombosis. In this Phase II study, we will characterize: 1) antithrombotic effects of AP4A analogue-16 in a rabbit intracarotid cannula thrombosis model, 2) biodistribution and blood clearance of the agent in the rabbits, and 3) toxicity of the agent in two species, rabbits and pigs. We believe that AP4A analogue-16 may prove to be a useful antithrombotic agent, arid in particular, when combined with other agents, may rove to be a major breakthrough in prevention of post-angioplasty arterial reocclusion. PROPOSED COMMERCIAL APPLICATION: This research will lead to development of a novel antithrombotic therapeutic agent. Antithrombotics serve a market in excess of $200 million per year in the United States.